Amylin

Insulin's Super Sidekick

Batman has Robin. The Lone Ranger has Tonto. And insulin has its own tough little partner: a hormone called amylin.

What’s that? You thought insulin worked alone, like Superman or Spiderman? Think again. Those guys only had madmen and criminals to fight. Insulin has the onerous task of keeping blood glucose in check while fending off challenges from food, stress, illness, and a slew of other hormones. However, like most sidekicks, amylin cannot replace or outperform insulin. Instead, it supplements insulin’s actions and allows insulin to do its job more effectively. This is particularly true after meals, when insulin by itself is no match for the blood glucose onslaught brought on by carbohydrates (sugars and starches) in the meal.

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How it works

As most people with diabetes already know, insulin helps transfer glucose out of the bloodstream and into the body’s cells. It is produced by a group of cells in the pancreas called beta cells. But beta cells secrete more than just insulin; they also secrete amylin. People with Type 1 diabetes, whose beta cells have been destroyed by the body’s immune system, secrete no amylin at all. And people with Type 2 diabetes who have progressed to the point of needing insulin injections (or infusions from a pump) have limited beta cell capacity and thus produce insufficient amylin.

So why all the fuss about amylin? Those of us with diabetes have survived for years without it. But the goal, of course, is more than just survival. It is to manage blood glucose levels effectively so that we feel good, can perform our daily routines, and live long, healthy, productive lives. The natural hormone amylin, as well as its synthetic equivalent, pramlintide (available since 2005 under the brand name Symlin), helps improve blood glucose control after meals. It does this by prompting the following actions:

Slowing digestion. Amylin slows gastric emptying, or movement of food from the stomach into the intestines. When carbohydrates stay in the stomach longer, they are converted to glucose and enter the bloodstream in a slower, more gradual manner.

Blocking glucagon secretion. Glucagon is a pancreatic hormone that raises the blood glucose level by stimulating the liver to release stored glucose. It is usually secreted in response to stress or hypoglycemia (low blood glucose). Without amylin, most people with diabetes produce extra glucagon when they eat; this can contribute to after-meal blood glucose spikes. When taken with meals, Symlin suppresses the inappropriate release of glucagon by the pancreas.

Enhancing satiety (the feeling of fullness). By helping to limit appetite and thus reduce the amount of food eaten during (and between) meals, amylin limits the potential for huge blood glucose spikes after eating.

So put it together: Symlin reduces mealtime glucagon secretion, slows digestion, and leads to decreased food consumption. This makes mealtime (rapid-acting) insulin’s job infinitely easier since there’s no dramatic blood glucose “spike” to deal with after eating. Instead, the blood glucose level tends to hold steady or rise only slightly after meals. Consequently, mealtime insulin requirements tend to decrease with Symlin use by an average of 10% to 20%, although this can vary considerably from person to person.

Overall, research shows that regular use of Symlin lowers the HbA1c level (a measure of long-term blood glucose control), the fasting blood glucose level, and blood triglyceride and cholesterol levels, and increases the percentage of time spent within one’s target blood glucose range. It also reduces blood glucose variability, or fluctuations in blood glucose level, which may be associated with long-term diabetes complications.

The US Food and Drug Administration has approved Symlin for use in adults with Type 1 or Type 2 diabetes who take rapid-acting insulin at meals. Although it is not yet approved for use in children, several studies have shown that Symlin is safe and effective when taken by adolescents in a supervised environment. Doctors have the option of prescribing Symlin off-label to children under the age of 18.

“Slimlin”?

Many people with diabetes have what could be described as an “insatiable appetite.” This may be due, at least in part, to the lack of amylin’s appetite-reducing effect. As a result, people with Type 1 as well as Type 2 diabetes can find it very challenging to lose unwanted weight.

Symlin can be a valuable tool in the “battle of the bulge.” Taking Symlin at meals helps create a sense of satisfaction and fullness, which can lead to eating smaller portions and taking fewer second helpings. And because Symlin’s effects tend to last for 2—3 hours, there is less of an urge to snack between meals. As a result, Symlin users lose an average of about six pounds over the first six months of taking the drug.

On the dark side

Every sidekick has his issues, and Symlin has its share. To start, Symlin is not available in pill form. It must be injected, just like insulin, at each meal (or whenever its effects are desired). Guidelines for storing and replacing injection pens or vials are also similar to those for insulin. But because it is somewhat acidic, Symlin cannot be mixed directly with insulin, and it may sting a bit when injected.

The most common side effect associated with Symlin is nausea. Approximately half of all people who try Symlin experience at least a mildly upset stomach. Symptoms tend to be more pronounced during Symlin’s peak action time, which is 15—30 minutes after injection. The discomfort usually lasts for only a few minutes and tends to subside before dissipating entirely after a few weeks of use.

For people who experience hypoglycemia unawareness (lack of low-blood-glucose warning signs) or are prone to severe hypoglycemia, Symlin may present some additional risks. Because food digests much more slowly when Symlin is taken, hypoglycemia can occur soon after meals, as premeal insulin starts working. It may therefore be necessary to reduce or delay mealtime insulin when taking Symlin. It is also not a good idea to take Symlin if your blood glucose level is low (or close to low) at the start of the meal, if you plan to exercise after the meal, or if the meal consists mostly of foods that digest slowly, such as pasta, legumes, or dairy products.

If hypoglycemia does occur, treating it can be a challenge. For the first hour or two after injection, Symlin blocks glucagon production and slows digestion considerably. Attempts to treat hypoglycemia with traditional methods may take a very long time to have any effect. Instead, glucose tablets or gel may need to be placed under the tongue so that some glucose is absorbed through the tissues of the mouth; otherwise, a glucagon injection may be necessary.

One other concern that comes with using Symlin is the titration process: determining the appropriate dose of Symlin, and then establishing the ideal dose and timing of mealtime insulin. Achieving a stable blood glucose level immediately after and between meals is a process that may take several weeks of trial and error.

Another concern is cost: Symlin is not cheap. Each box of Symlin pens costs more than an equivalent box of rapid-acting insulin pens. Most major health insurance plans cover Symlin for people with Type 1 or Type 2 diabetes who take mealtime insulin, but copays usually apply, and preauthorization is almost always necessary. That typically means paperwork, waiting, and more paperwork before coverage takes effect. A patient assistance program is available through the manufacturer of Symlin (Amylin Pharmaceuticals) for people who have difficulty affording the product.

Strategies for success

Sidekicks often experience a “breaking-in period.” For example, it took a while for Ed McMahon to learn to wait for the punch line before laughing at Johnny Carson’s jokes on the old Tonight Show. Symlin is no different. It takes some practice and effort to get Symlin to work right – but once it does, the benefits can be significant.

Through years of personal and professional/clinical experience with Symlin, I have had the opportunity to learn what tends to work and what does not. Here are some recommendations and observations:

1. Start out using Symlin at only one meal, such as breakfast. Once the dose of Symlin and appropriate adjustments to the dose of mealtime insulin are determined, apply the same strategies to your other meals. Unlike insulin, the dose of Symlin does not vary from meal to meal; the same dose is taken regardless of what is eaten. And adjustments made to insulin’s dose size and timing should work consistently whenever Symlin is taken.

2. Take Symlin 5—10 minutes before your meal, and take your insulin 5—10 minutes after finishing your meal. This will help ensure that the Symlin is working at the right time, so that the insulin will not peak too soon and cause post-meal hypoglycemia. If you start to see a drop in your blood glucose level soon after eating followed by a significant rise a few hours later, consider switching to Regular insulin – or, if you use an insulin pump, delivering the insulin bolus over 1—2 hours. (Regular insulin starts working in 30—45 minutes, compared to 10—15 minutes for rapid-acting insulin analogs.)

3. When starting with Symlin, reduce your usual dose of mealtime insulin by about 25%. Symlin’s package insert recommends an initial 50% reduction; however, in clinical practice, most Symlin users settle on only a 10% to 20% reduction in mealtime insulin. A 25% reduction is a safe and reasonable starting point.

4. Settle on a Symlin dose before finalizing your insulin adjustments. Start with the lowest dose of Symlin (15 mcg) and increase in 15-mcg increments until an effective dose is reached. The right dose of Symlin will either cause an unusual “full” or “sour stomach” sensation 15—30 minutes after injection, or result in a reasonably constant blood glucose level for a few hours after eating. If neither of these occurs, the dose of Symlin needs to be increased. Get in the habit of checking your blood glucose level an hour after eating while adjusting your Symlin and insulin doses (or check your trends on a continuous glucose monitor).

5. The Symlin dose may need to be increased over time. After using it for several months or years, many people develop a tolerance to Symlin, and the dose may need to be increased slightly to achieve the same results as earlier.

Symlin delivery options

Symlin is most commonly given by injection pen. Symlin pens allow giving the drug in 15-, 30-, 45-, 60-, or 120-mcg doses. The low-dose (starter) pen delivers 15, 30, 45 or 60 mcg; the high-dose pen delivers 60 or 120 mcg. Because Symlin needs to be injected just below the skin, it is generally recommended that short (5- or 6-mm) needles be used.

Some people require doses higher than 120 mcg or less than 15 mcg; others need doses that are in between the preset pen increments. For these individuals, Symlin is available in vials for injection with a syringe. (One unit on an insulin syringe denotes 6 mcg of Symlin; 2.5 units would be 15 mcg, and so on.) However, the vials will be phased out by December 31, 2010.

Some people who use Symlin have opted to deliver it through an insulin pump. Limited research has been conducted on this topic, but available reports indicate that pumps can be a safe and effective method of delivering mealtime boluses of Symlin. However, some basal delivery may be necessary to prevent clogs from forming in the tube and cannula.

A partner at last

After more than 80 years of going it alone, it’s nice to know that insulin is finally getting some well-deserved help. But is Symlin right for you? That decision is a personal one to be made with your doctor. Symlin certainly warrants consideration if you need to lose weight or if you want better control over your after-meal blood glucose levels. The transition to using Symlin is easiest if you have a doctor or diabetes educator who is familiar and comfortable with the drug. But even if this is not the case, don’t hesitate to ask about Symlin – you and your team can learn about it together. (Amylin Pharmaceuticals offers a free patient support program by phone and e-mail that features a nurse who can answer questions and offer general guidance. To enroll, call [888] 796-5461 or visit www.symlinsupport.com.) Just be prepared to deal with the potential side effects of Symlin, and recognize that some trial and error will be necessary to get it working for you. In the end, you may wonder how you ever lived without such a terrific little helper.

Gary Scheiner is a Certified Diabetes Educator with a private practice, Integrated Diabetes Services LLC (www.integrateddiabetes.com), based near Philadelphia. He and his staff counsel individuals with diabetes throughout the world on intensive management by phone and Internet. He can be reached at (877) 735-3648 or gary@integrateddiabetes.com.

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